P1170: INCIDENCE, TREATMENT AND OUTCOME OF PATIENTS WITH RICHTER’S SYNDROME: A POPULATION-BASED COHORT STUDY IN THE NETHERLANDS
Authors: F. Huisman, D. Al-sarayfi, M. Bellido, R. Mous, J. S. Vermaat, A. P. Kater, M. Nijland, M. Brink
Journal: HemaSphere (2022)

Background: Richter’s syndrome is a rare aggressive transformation of chronic lymphocytic leukaemia (CLL) into a diffuse large B-cell lymphoma (RS-DLBCL) or Hodgkin lymphoma. Patients with RS-DLBCL have an average overall survival (OS) of 6-12 months. Survival of RS-DLBCL patients previously treated for their CLL is inferior as compared to patients with a previously untreated CLL. In recent years, management of CLL has changed with the introduction of novel agents. Aims: This study evaluates the clinical characteristics, treatment and survival of RS-DLBCL patients in a contemporary era of CLL management in the Netherlands. Methods: DLBCL patients ≥18 years diagnosed in 2014-2020 were identified in the Netherlands Cancer Registry (NCR), with survival follow-up through February 1st, 2021. A prior CLL, diagnosed in 2014-2019, was identified through cross-linkage with the NCR. For these patients, detailed information on CLL and RS-DLBCL treatment was available. Patients with CLL and DLBCL diagnosis within a time interval of 3 months were defined as concurrent RS-DLBCL (concurrent RS). The primary endpoint was overall survival (OS). OS was defined as the time between diagnosis and death from any cause and presented for three subgroups of RS-DLBCL patients, 1) concurrent RS, 2) RS-DLBCL following treated CLL (treated RS), and 3) RS-DLBCL following untreated CLL (untreated RS). Results: A total of 110 patients with RS-DLBCL (median age 72 years, range 43-89 years; 61% males) were selected, including 22 (20%) concurrent RS, 38 (35%) treated RS, and 50 (45%) untreated RS. The majority of patients were diagnosed with stage III/IV RS-DLBCL, i.e., 55% of the concurrent RS were diagnosed with advanced disease as compared to 70% and 79% of the untreated and treated RS, respectively. Median time from CLL to RS diagnosis was for untreated RS 23.2 months (range, 3.4-74.4 months) and for treated RS 17.4 months (range, 4.7-67.5 months). Of the 38 treated RS patients, 30 patients had received rituximab in combination with either chlorambucil (n=11), purine analogues (n=8) or chemotherapeutic regimens such as cyclophosphamide-vincristine-prednisolonie (n=11). Seven patients received treatment including ibrutinib or venetoclax, and 3 patients received treatment not including one or more of the abovementioned regimens. Regarding primary treatment of all RS-DLBCL patients, 19 (86%) out of 22 concurrent RS patients received R-CHO(E)P, 2 patients received another R-based chemotherapy, and 1 patient did not receive therapy. Of the 88 (un)treated RS patients, 59 (67%) received R-CHO(E)P of whom 6 patients were consolidated with autologous stem cell transplantation (SCT) and 2 patients with allogenic SCT. Of the 29 remaining patients, 17 (19%) were treated with a R-based chemotherapy regimen including R-PECC and R-bendamustine, and 12 (14%) patients did not receive therapy. The overall response rate (≥partial remission) of concurrent RS patients was superior as compared to untreated and treated RS patients (86% vs. 70% vs. 55%, respectively; p<0.01). With a median follow-up of 9.5 months (range 0.3-78.3), 3-years OS was 64% for patients with concurrent RS, 53% for untreated RS patients and 5% for treated RS patients (Figure; p<0.01). Image:Summary/Conclusion: In this contemporary population-based study, concurrent RS patients have superior OS, while survival among treated RS patients is very poor. Our data underline the importance of development of new strategies, specifically aiming at treated RS patients.